tbuckley/cabot-search huggingface dataset:
Digital lifestyle treatment improves long-term metabolic control in type 2 diabetes with different effects in pathophysiological and genetic subgroups
Authors: Vishal A. Salunkhe, Neha Sinha, Emma Ahlqvist, Rashmi B. Prasad, Svetlana Johansson, Birgitta Abrahamsson, Anders H. Rosengren
Journal: npj Digital Medicine (2023)

Abstract To address the unmet need for scalable solutions for lifestyle treatment, we developed a new digital method to promote behavioral change. Here we report that patients with type-2 diabetes in Sweden ( n = 331) exposed to the intervention have significantly improved HbA1c during a median follow-up of 1038 days (4 mmol/mol compared with matched controls; P = 0.009). This is paralleled by reduced body weight, ameliorated insulin secretion, increased physical activity, and cognitive eating restraints. Participants with high BMI and insulin resistance have an even larger response, as have non-risk allele carriers for the FTO gene. The findings open a new avenue for scalable lifestyle management with sustained efficacy and highlight a previously unrecognized opportunity for digital precision treatment based on genetics and individual pathophysiology. ClinicalTrials.gov NCT04624321.
Proteomics uncovers molecular features for relapse risk stratification in patients with diffuse large B-cell lymphoma
Authors: Maja Ludvigsen, Amanda Jessica Campbell, Marie Beck Enemark, Trine Engelbrecht Hybel, Marja-Liisa Karjalainen-Lindsberg, Klaus Beiske, Mette Bjerre, Lars Møller Pedersen, Harald Holte, Sirpa Leppä, Judit Meszaros Jørgensen, Bent Honoré
Journal: Blood Cancer Journal (2023)

Proteomics uncovers molecular features for
A potent and broad‐spectrum neutralizing nanobody for SARS‐CoV‐2 viruses, including all major Omicron strains
Authors: Hebang Yao, Hongyang Wang, Zhaoyong Zhang, Yuchi Lu, Zhiying Zhang, Yu Zhang, Xinyi Xiong, Yanqun Wang, Zhizhi Wang, Haitao Yang, Jincun Zhao, Wenqing Xu
Journal: MedComm (2023)

SARS-CoV-2 viruses are highly transmissible and immune evasive. It is critical to develop broad-spectrum prophylactic and therapeutic antibodies for potential future pandemics. Here, we used the phage display method to discover nanobodies (Nbs) for neutralizing SARS-CoV-2 viruses especially Omicron strains. The leading nanobody (Nb), namely, Nb4, with excellent physicochemical properties, can neutralize Delta and Omicron subtypes, including BA.1, BA.1.1 (BA.1 + R346K), BA.2, BA.5, BQ.1, and XBB.1. The crystal structure of Nb4 in complex with the receptor-binding domain (RBD) of BA.1 Spike protein reveals that Nb4 interacts with an epitope on the RBD overlapping with the receptor-binding motif, and thus competes with angiotensin-converting enzyme 2 (ACE2) binding. Nb4 is expected to be effective for neutralizing most recent Omicron variants, since the epitopes are evolutionarily conserved among them. Indeed, trivalent Nb4 interacts with the XBB1.5 Spike protein with low nM affinity and competes for ACE2 binding. Prophylactic and therapeutic experiments in mice indicated that Nb4 could reduce the Omicron virus loads in the lung. In particular, in prophylactic experiments, intranasal administration of multivalent Nb4 completely protected mice from Omicron infection. Taken together, these results demonstrated that Nb4 could serve as a potent and broad-spectrum prophylactic and therapeutic Nb for COVID-19.
Cystic fibrosis and the cardiovascular system: the unexpected heartache
Authors: Helge Hebestreit, Christina S. Thornton
Journal: European Respiratory Journal (2023)

In recent years, advancements in medical care and therapies have significantly improved the life expectancy of individuals with cystic fibrosis (CF). As a result, an increasing number of people with CF are now reaching adulthood and experience the long-term consequences of the disease. One of the emerging challenges faced by this growing population is the increased risk of cardiac disease [1]. The rate of cardiovascular disease (CVD) in CF varies among individuals and studies, and the exact prevalence is not well-established. Indeed, a higher body mass index (BMI), lipid metabolism and smoking, all traditional cardiac risk factors, are often attenuated in CF disease [2]. However, it is generally recognised that people with CF have an increased risk of developing cardiovascular complications compared to the general population, which historically has been associated as secondary to progressive lung disease and respiratory failure. Other factors, including presence of CF-related diabetes, high salt dietary intake, chronic kidney disease and chronic inflammation ( i.e. similar to those of other chronic diseases, including HIV, rheumatoid arthritis and systemic lupus erythematosus) all render cardiac risk in this population [2]. Studies have reported varying prevalence rates of CVD, ranging from around 10% to 30% in the CF population. The most common cardiovascular conditions seen in CF patients include atherosclerosis, hypertension and heart failure; however, other clinical sequalae include effects on the aorta, pulmonary hypertension, and peripheral vascular disease [1]. More recently, a multicentre retrospective cohort of people with CF and SARS-CoV-2 infection (n=422) reported that nearly half had a history of diabetes (47%) or hypertension (48%) [3]. Furthermore, 22.5% had a history of ischaemic heart disease, suggesting that CVD might be under-reported in this population. Finally, all reported cardiac risk factors were significantly higher in people with CF compared to those without CF (all p-values <0.01). Consequently, there is a need for proactive cardiac monitoring and management in people with CF to identify and address cardiovascular risk factors early on. Several mechanisms underpin CVD risk in CF [4]. One is via chronic hypoxaemia in CF caused by ventilation heterogeneity and destruction of lung tissue, leading to pulmonary vasoconstriction, pulmonary hypertension and cor pulmonale. A second is through the presence of cystic fibrosis transmembrane conductance regulator (CFTR) protein in cardiac myocytes, including atrial and ventricular myocytes, as well as blood vessels. Similar to its role in epithelial cells, CFTR in the heart plays a role in chloride ion conduction. Finally, the loss of CFTR function can impact myocyte contractility, intracellular calcium signalling, myocardial fibrosis and heart remodelling. Evaluation of the cardiovascular system is important in cystic fibrosis patients <https://bit.ly/444uK6Y>
Carbon monoxide poisoning: largely preventable
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2023)

The quality of air inside homes, private and public buildings is an essential determinant of health and people's wellbeing. Hazardous substances linked to human activities, such as combustion of fuels for cooking or heating, can lead to a broad range of health issues. Household air pollution and its effects is well recognised in health, but the particular issue of carbon monoxide poisoning has received little attention.
Individual-level risk factors for suicide mortality in the general population: an umbrella review
Authors: Louis Favril, Rongqin Yu, John R Geddes, Seena Fazel
Journal: The Lancet Public Health (2023)

Deaths by suicide remain a major public health challenge worldwide. Identifying and targeting risk factors for suicide mortality is a potential approach to prevention. We aimed to summarise current knowledge on the range and magnitude of individual-level risk factors for suicide mortality in the general population and evaluate the quality of the evidence.
A novel modelling approach to assess obesity prevention at the population level: limitations and opportunities
Authors: Li Ming Wen
Journal: The Lancet Public Health (2023)

Obesity prevention and treatment interventions in childhood have become paramount due to an increase in the prevalence of childhood obesity worldwide1,2 and its associated long-term health consequences.3 However, many efforts have been made to find effective prevention and treatment programmes for obesity in children, which is encouraging. For example, in children aged 0–5 years, the Healthy Beginnings trial4 and its related CHAT trial5 used nurse-led home visits or telephone calls to support parents and their children aged 0–2 years or 2–3 years, which led to a statistically significant 0·29 kg/m2 lower mean BMI of these children compared with children in the control group and 0·59 kg/m2 lower mean BMI of these children compared with children from households with lower income.
Management of de Quervain Tenosynovitis
Authors: Dimitris Challoumas, Rohan Ramasubbu, Elliot Rooney, Emily Seymour-Jackson, Amit Putti, Neal L. Millar
Journal: JAMA Network Open (2023)

Importance There is a plethora of treatment options for patients with de Quervain tenosynovitis (DQT), but there are limited data on their effectiveness and no definitive management guidelines. Objective To assess and compare the effectiveness associated with available treatment options for DQT to guide musculoskeletal practitioners and inform guidelines. Data Sources Medline, Embase, PubMed, Cochrane Central, Scopus, OpenGrey.eu, and WorldCat.org were searched for published studies, and the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, The European Union Clinical Trials Register, and the ISRCTN registry were searched for unpublished and ongoing studies from inception to August 2022. Study Selection All randomized clinical trials assessing the effectiveness of any intervention for the management of DQT. Data Extraction and Synthesis This study was prospectively registered on PROSPERO and conducted and reported per Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA) and PRISMA in Exercise, Rehabilitation, Sport Medicine and Sports Science (PERSIST) guidance. The Cochrane Risk of Bias tool and the Grading of Recommendations, Assessment, Development, and Evaluations tool were used for risk of bias and certainty of evidence assessment for each outcome. Main Outcomes and Measures Pairwise and network meta-analyses were performed for patient-reported pain using a visual analogue scale (VAS) and for function using the quick disabilities of the arm, shoulder, and hand (Q-DASH) scale. Mean differences (MD) with their 95% CIs were calculated for the pairwise meta-analyses. Results A total of 30 studies with 1663 patients (mean [SD] age, 46 [7] years; 80% female) were included, of which 19 studies were included in quantitative analyses. From the pairwise meta-analyses, based on evidence of moderate certainty, adding thumb spica immobilization for 3 to 4 weeks to a corticosteroid injection (CSI) was associated with statistically but not clinically significant functional benefits in the short-term (MD, 10.5 [95% CI, 6.8-14.1] points) and mid-term (MD, 9.4 [95% CI, 7.0-11.9] points). In the network meta-analysis, interventions that included ultrasonography-guided CSI ranked at the top for pain. CSI with thumb spica immobilization had the highest probability of being the most effective intervention for short- and mid-term function. Conclusions and Relevance This network meta-analysis found that adding a short period of thumb spica immobilization to CSI was associated with statistically but not clinically significant short- and mid-term benefits. These findings suggest that administration of CSI followed by 3 to 4 weeks immobilization should be considered as a first-line treatment for patients with DQT.
<i>Notes from the Field</i>: Early Identification of the SARS-CoV-2 Omicron BA.2.86 Variant by the Traveler-Based Genomic Surveillance Program — Dulles International Airport, August 2023
Authors: Stephen M. Bart, Andrew P. Rothstein, Casandra W. Philipson, Teresa C. Smith, Birgitte B. Simen, Azaibi Tamin, Lydia J. Atherton, Jennifer L. Harcourt, Allison Taylor Walker, Daniel C. Payne, Ezra T. Ernst, Robert C. Morfino, Ian Ruskey, Cindy R. Friedman
Journal: MMWR Morbidity and Mortality Weekly Report (2023)
Landscape of Baseline and Acquired Genomic Alterations in Circulating Tumor DNA with Abemaciclib Alone or with Endocrine Therapy in Advanced Breast Cancer
Authors: Matthew P. Goetz, Erika P. Hamilton, Mario Campone, Sara A. Hurvitz, Javier Cortes, Stephen Johnston, Antonio Llombart-Cussac, Peter A. Kaufman, Masakazu Toi, Guy Jerusalem, Hillary Graham, Hong Wang, Valerie M. Jansen, Lacey M. Litchfield, Miguel Martin
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To identify potential predictors of response and resistance mechanisms in patients with hormone receptor–positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC) treated with the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib ± endocrine therapy (ET), baseline and acquired genomic alterations in circulating tumor DNA (ctDNA) were analyzed and associated with clinical outcomes. Experimental Design: MONARCH 3: postmenopausal women with HR+, HER2− ABC and no prior systemic therapy in the advanced setting were randomly assigned to abemaciclib or placebo plus nonsteroidal aromatase inhibitor (NSAI). nextMONARCH: women with HR+, HER2− metastatic breast cancer that progressed on/after prior ET and chemotherapy were randomly assigned to abemaciclib alone (two doses) or plus tamoxifen. Baseline and end-of-treatment plasma samples from patients in MONARCH 3 and nextMONARCH (monotherapy arms) were analyzed to identify somatic genomic alterations. Association between genomic alterations and median progression-free survival (mPFS) was assessed. Results: Most patients had ≥1 genomic alteration detected in baseline ctDNA. In MONARCH 3, abemaciclib+NSAI was associated with improved mPFS versus placebo+NSAI, regardless of baseline alterations. ESR1 alterations were less frequently acquired in the abemaciclib+NSAI arm than placebo+NSAI. Acquired alterations potentially associated with resistance to abemaciclib ± NSAI included RB1 and MYC. Conclusions: In MONARCH 3, certain baseline ctDNA genomic alterations were prognostic for ET but not predictive of abemaciclib response. Further studies are warranted to assess whether ctDNA alterations acquired during abemaciclib treatment differ from other CDK4/6 inhibitors. Findings are hypothesis generating; further exploration is warranted into mechanisms of resistance to abemaciclib and ET. See related commentary by Wander and Bardia, p. 2008
Reply to Drs. Hamo and Samo
Authors: Sanne N. van Munster, Raf Bisschops
Journal: Endoscopy (2023)

See also: Detection of Barrett's dysplasia using forceps biopsies vs. wide-area transepithelial samplingEndoscopy 2023; 55(11): 1055-1055DOI: 10.1055/a-2094-7940
Fibroblast growth factor 10 reverses cigarette smoke- and elastase-induced emphysema and pulmonary hypertension in mice
Authors: Stefan Hadzic, Cheng-Yu Wu, Marija Gredic, Oleg Pak, Edma Loku, Simone Kraut, Baktybek Kojonazarov, Jochen Wilhelm, Monika Brosien, Mariola Bednorz, Michael Seimetz, Andreas Günther, Djuro Kosanovic, Natascha Sommer, David Warburton, Xiaokun Li, Friedrich Grimminger, Hossein A. Ghofrani, Ralph T. Schermuly, Werner Seeger, Elie El Agha, Saverio Bellusci, Norbert Weissmann
Journal: European Respiratory Journal (2023)

COPD is an incurable disease and a leading cause of death worldwide. In mice, fibroblast growth factor (FGF)10 is essential for lung morphogenesis, and in humans, polymorphisms in the human FGF10 gene correlate with an increased susceptibility to develop COPD.We analysed FGF10 signalling in human lung sections and isolated cells from healthy donor, smoker and COPD lungs. The development of emphysema and PH was investigated in Fgf10+/- and Fgfr2b+/- (FGF receptor 2b) mice upon chronic exposure to cigarette smoke. In addition, we overexpressed FGF10 in mice following elastase- or cigarette smoke-induced emphysema and pulmonary hypertension (PH).We found impaired FGF10 expression in human lung alveolar walls and in primary interstitial COPD lung fibroblasts. In contrast, FGF10 expression was increased in large pulmonary vessels in COPD lungs. Consequently, we identified impaired FGF10 signalling in alveolar walls as an integral part of the pathomechanism that leads to emphysema and PH development: mice with impaired FGF10 signalling (Fgf10+/- and Fgfr2b+/- ) spontaneously developed lung emphysema, PH and other typical pathomechanistic features that generally arise in response to cigarette smoke exposure.In a therapeutic approach, FGF10 overexpression successfully restored lung alveolar and vascular structure in mice with established cigarette smoke- and elastase-induced emphysema and PH. FGF10 treatment triggered an initial increase in the number of alveolar type 2 cells that gradually returned to the basal level when the FGF10-mediated repair process progressed. Therefore, the application of recombinant FGF10 or stimulation of the downstream signalling cascade might represent a novel therapeutic strategy in the future.
Perceptions of Factors Associated With Sustainability of Health Care Innovation Centers
Authors: Holly Krelle, Michael Martinez, Kira Garry, Leora I. Horwitz
Journal: JAMA Network Open (2023)

Importance Innovation centers in US health care systems are increasingly common but variably successful and sustainable. Few studies have examined how and why some centers achieve sustainable success but others do not. Objective To explore whether and how innovation centers in US health care systems are able to successfully sustain themselves over multiple years. Design, Setting, and Participants In this qualitative study, semistructured, qualitative interviews of leaders at 9 innovation centers across the US were conducted from January 1, 2019, to December 31, 2020. Data analysis was conducted from December 2020 to April 2021 using qualitative methods and a deductive framework based on the Consolidated Framework for Implementation Research. Centers were identified through purposeful sampling. The 9 study centers had a mean age of 6 years (range, 2-15 years); most were affiliated with an academic teaching hospital and half with a medical school. Two were wholly separate from the health care system. Two-thirds had fewer than 10 full-time staff members. Exposures All interviewees were staff of a US-based innovation center. This study did not evaluate particular interventions or innovations. Main Outcomes and Measures Perceptions of and views on factors associated with the success and sustainability of innovation centers. Results Staff interviewed at 9 innovation centers across the US described 3 key activities that appeared to be associated with long-term sustainability: facilitating innovation projects that were valued for quality improvement and cost avoidance, not just return on investment; acting as networking nodes for their institutions; and upskilling staff. These activities were associated with improved institutional culture. Two structural characteristics underpinned successful centers: finding an effective balance between being “internal” and being “external” to the organization and providing practical support and skills otherwise lacking within the wider institution. Conclusions and Relevance This qualitative study of 9 innovation centers explored how centers sustained themselves within US health care institutions and showed that success was often associated with interpersonal relationships and cultural benefits. Independent financial sustainability was not always essential to longevity; systems also valued how centers could create cultures of innovation and upskill staff.
Routine Vaccination Coverage — Worldwide, 2022
Authors: Gurpreet Kaur, M. Carolina Danovaro-Holliday, George Mwinnyaa, Marta Gacic-Dobo, Lauren Francis, Jan Grevendonk, Samir V Sodha, Ciara Sugerman, Aaron Wallace
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In 2020, the World Health Assembly endorsed the Immunization Agenda 2030 (IA2030), the 2021-2030 global strategy that envisions a world where everyone, everywhere, at every age, fully benefits from vaccines. This report reviews trends in World Health Organization and UNICEF immunization coverage estimates at global, regional, and national levels through 2022 and documents progress toward improving coverage with respect to the IA2030 strategy, which aims to reduce the number of children who have not received the first dose of a diphtheria-tetanus-pertussis-containing vaccine (DTPcv1) worldwide by 50% and to increase coverage with 3 diphtheria-tetanus-pertussis-containing vaccine doses (DTPcv3) to 90%. Worldwide, coverage ≥1 dose of DTPcv1 increased from 86% in 2021 to 89% in 2022 but remained below the 90% coverage achieved in 2019. Estimated DTPcv3 coverage increased from 81% in 2021 to 84% in 2022 but also remained below the 2019 coverage of 86%. Worldwide in 2022, 14.3 million children were not vaccinated with DTPcv1, a 21% decrease from 18.1 million in 2021, but an 11% increase from 12.9 million in 2019. Most children (84%) who did not receive DTPcv1 in 2022 lived in low- and lower-middle-income countries. COVID-19 pandemic-associated immunization recovery occurred in 2022 at the global level, but progress was unevenly distributed, especially among low-income countries. Urgent action is needed to provide incompletely vaccinated children with catch-up vaccinations that were missed during the pandemic, restore national vaccination coverage to prepandemic levels, strengthen immunization programs to build resiliency to withstand future unforeseen public health events, and further improve coverage to protect children from vaccine-preventable diseases.
Time to Treat the Climate and Nature Crisis as One Indivisible Global Health Emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Gregory E. Erhabor, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal: The American Journal of Bioethics (2023)
Neuronal types in the mouse amygdala and their transcriptional response to fear conditioning
Authors: Hannah Hochgerner, Shelly Singh, Muhammad Tibi, Zhige Lin, Niv Skarbianskis, Inbal Admati, Osnat Ophir, Nuphar Reinhardt, Shai Netser, Shlomo Wagner, Amit Zeisel
Journal: Nature Neuroscience (2023)

Abstract The amygdala is a brain region primarily associated with emotional response. The use of genetic markers and single-cell transcriptomics can provide insights into behavior-associated cell state changes. Here we present a detailed cell-type taxonomy of the adult mouse amygdala during fear learning and memory consolidation. We perform single-cell RNA sequencing on naïve and fear-conditioned mice, identify 130 neuronal cell types and validate their spatial distributions. A subset of all neuronal types is transcriptionally responsive to fear learning and memory retrieval. The activated engram cells upregulate activity-response genes and coordinate the expression of genes associated with neurite outgrowth, synaptic signaling, plasticity and development. We identify known and previously undescribed candidate genes responsive to fear learning. Our molecular atlas may be used to generate hypotheses to unveil the neuron types and neural circuits regulating the emotional component of learning and memory.
<i>QuickStats:</i> Percentage* of Children and Adolescents Aged 5–17 Years Who Took Medication for Their Mental Health or Received Counseling or Therapy from a Mental Health Professional During the Past 12 Months,† by Year — National Health Interview Survey,§ United States, 2019 and 2022
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

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